Figure 5 - uploaded by Akiko Furuta
Content may be subject to copyright.
Double immunofluorescence of P21 rat cerebral neocortex for NDRG1 ( A : FITC, green) and GFAP ( B : Texas red, red), and the merged image ( C ). Overlapping of NDRG1 and GFAP is indicated by yellow. Bar ϭ 10 m.
Source publication
N-myc downregulated gene 1 (NDRG1) is a 43-kD protein whose mRNA is induced by DNA damage, hypoxia, or prolonged elevation of intracellular calcium. Although NDRG1 is also upregulated during cell differentiation, there are few studies on NDRG1 expression during postnatal development. Here we investigated the expression and cellular distribution of...
Similar publications
Constitutive activation of the NF-κB pathway is associated with diffuse large B-cell lymphoma (DLBCL) pathogenesis, but whether microRNA dysfunction can contribute to these events remains unclear. Starting from an integrative screening strategy, we uncovered that the negative NF-κB regulator TNFAIP3 is a direct target of miR-125a and miR-125b, whic...
The human family of MAPK (mitogen-activated protein kinase) signal-integrating kinases (Mnks) comprises four related proteins derived from two genes by alternative splicing. The MNK1 gene gives rise to two proteins, Mnk1a and Mnk1b, which possess distinct C-termini and properties. Despite lacking the C-terminal MAPK-binding site, Mnk1b shows higher...
Proteins of the transmembrane (or T cell) Ig and mucin domain (TIM) family are expressed by multiple cell types within the immune systems of rodents and humans. Studies over the last several years have suggested that these proteins may be promising targets for therapeutic manipulation of immune responses. This review discusses the progress that has...
WNT1-inducible signaling pathway protein-1 (WISP1), a member of the CYR61/CTGF/Nov family of growth factors, can mediate cell growth, transformation, and survival. Previously we demonstrated that WISP1 is up-regulated in post-infarct heart, stimulates cardiac fibroblast proliferation, and is induced by the proinflammatory cytokine tumor necrosis fa...
Citations
... Hence, NDRG1 undergoes down-regulation in a number of human cancers including breast, prostate and pancreatic cancers (Cangul, 2004;Angst et al., 2006;Pflueger et al., 2009;Nagai et al., 2011). Although there is a wealth of knowledge about the expression profile of NDRG1 gene in cancer, especially the metastatic cases (Wakisaka et al., 2003;Maruyama et al., 2006;Ureshino et al., 2012), the importance of the single nucleotide polymorphisms (SNPs) located in NDRG1 gene is quite unclear. ...
Background and purpose
One of the most prevalent cancers in the world and Iran is gastric cancer with a high degree of lethality. There are many environmental factors and genes responsible for gastric cancer incidence. Among genetics factors, NDRG1 has been reported to be associated with the gastric cancer progression, while its single nucleotide polymorphisms (SNPs) have not been widely studied. Among the SNPs, rs1049694 might be of interest as it is located in the 3′UTR of NDRG1 transcripts. However, the relevance of rs1049694 with the incidence of gastric cancer has not been studied yet.
Materials and methods
In this study, 144 patients with gastric cancer and 66 healthy individuals were selected. After taking blood samples and extraction of genomic DNA, genotyping was performed on 1049694 using allele specific primer (ASP)-PCR method. The data were analyzed with the SNPStats and SPSS.
Results
The results showed that 3 different genotypes were found in gastric cancer rs1049694 NDRG1 gene polymorphism. The rs1049694 allele G was significantly associated with the higher risk of gastric cancer and metastasis.
Conclusion
The presence of allele G at the rs1049694 position located in NDRG1 gene is significantly associated with the higher risk of gastric cancer. This allele was significantly observed higher in the metastatic patients. This SNP might be studied further to be considered as a biomarker for diagnosis/prognosis of gastric cancer.
... NDRG members have been found to be widely and highly expressed in mammalian brains [13,18,19]. Okuda et al. [20] used specific antibodies to distinguish NDRG family members from each other and analyzed their cellular distribution pattern in the mouse brain. ...
Human N-myc downstream-regulated gene 2 (NDRG2) has been shown to be a multifunctional protein associated with cell proliferation, differentiation, transmembrane transport, and stress responses. In most mammalian brains, NDRG2 is principally expressed in astrocytic cells throughout different regions. NDRG2 has been increasingly implicated in the regulation of neurogenesis and in the development of nervous system diseases, including neurodegeneration, ischemia, and glioblast-oma. This review summarizes the distribution and subcellular localization of NDRG2 in brain tissues, highlights the physiological actions of NDRG2 in the nervous system, and further discusses the roles of NDRG2 during the occurrence and development of several nervous system diseases.
... This could reflect the differentiation that hippocampal neurons and astrocytes undergo, as hippocampal neurons go through morphological and metabolic changes in the first two postnatal weeks when NDRG1 is expressed, after which NDRG1 expression arises in mature GFAP-positive astrocytes. This suggests that NDRG1 could play a role in the process of differentiation [19]. ...
The N-Myc downstream-regulated gene (NDRG) family consists of four members (NDRG1, NDRG2, NDRG3, NDRG4) that are differentially expressed in various organs and function in important processes, like cell proliferation and differentiation. In the last couple of decades, interest in this family has risen due to its connection with several disorders of the nervous system including Charcot-Marie-Tooth disease and dementia, as well as nervous system cancers. By combining a literature review with in silico data analysis of publicly available datasets, such as the Mouse Brain Atlas, BrainSpan, the Genotype-Tissue Expression (GTEx) project, and Gene Expression Omnibus (GEO) datasets, this review summarizes the expression and functions of the NDRG family in the healthy and diseased nervous system. We here show that the NDRGs have a differential, relatively cell type–specific, expression pattern in the nervous system. Even though NDRGs share functionalities, like a role in vesicle trafficking, stress response, and neurite outgrowth, other functionalities seem to be unique to a specific member, e.g., the role of NDRG1 in myelination. Furthermore, mutations, phosphorylation, or changes in expression of NDRGs are related to nervous system diseases, including peripheral neuropathy and different forms of dementia. Moreover, NDRG1, NDRG2, and NDRG4 are all involved in cancers of the nervous system, such as glioma, neuroblastoma, or meningioma. All in all, our review elucidates that although the NDRGs belong to the same gene family and share some functional features, they should be considered unique in their expression patterns and functional importance for nervous system development and neuronal diseases.
... The specific role of CRMP1 in CCD with epilepsy needs further evaluation. NDRG1 is upregulated during cell differentiation, and its cellular distribution and molecular assembly changes with postnatal development, which is correlated with the maturation of brain [33]. NDRG1 exists in oligodendrocytes in cerebrum and decreases significantly at the end stage of myelin degradation [34,35], and its mutation is found related to subcortical white matter abnormalities and severe demyelinating neuropathy [36]. ...
Cortical dysplasia accounts for at least 14% of epilepsy cases, and is mostly seen in children. However, the understanding of molecular mechanisms and pathogenesis underlying cortical dysplasia is limited. The aim of this cross-sectional study is to identify potential key molecules in the mechanisms of cortical dysplasia by screening the proteins expressed in brain tissues of childhood cortical dysplasia patients with epilepsy using isobaric tags for relative and absolute quantitation-based tandem mass spectrometry compared to controls, and several differentially expressed proteins that are not reported to be associated with cortical dysplasia previously were selected for validation using real-time polymerase chain reaction, immunoblotting and immunohistochemistry. 153 out of 3340 proteins were identified differentially expressed between childhood cortical dysplasia patients and controls. And FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, and FABP3 were selected for validation and identified to be increased in childhood cortical dysplasia patients, while PRDX6 and PSAP were identified decreased. This is the first report on differentially expressed proteins in childhood cortical dysplasia. We identified differential expression of FSCN1, CRMP1, NDRG1, DPYSL5, MAP4, FABP3, PRDX6 and PSAP in childhood cortical dysplasia patients, these proteins are involved in various processes and have various function. These results may provide new directions or targets for the research of childhood cortical dysplasia, and may be helpful in revealing molecular mechanisms and pathogenesis and/or pathophysiology of childhood cortical dysplasia if further investigated.
... NDRG members have been found to be widely and highly expressed in mammalian brains [13,18,19]. Okuda et al. [20] used specific antibodies to distinguish NDRG family members from each other and analyzed their cellular distribution pattern in the mouse brain. ...
Human N-myc downstream-regulated gene 2 (NDRG2) has been shown to be a multifunctional protein associated with cell proliferation, differentiation, transmembrane transport, and stress responses. In most mammalian brains, NDRG2 is principally expressed in astrocytic cells throughout different regions. NDRG2 has been increasingly implicated in the regulation of neurogenesis and in the development of nervous system diseases, including neurodegeneration, ischemia, and glioblastoma. This review summarizes the distribution and subcellular localization of NDRG2 in brain tissues, highlights the physiological actions of NDRG2 in the nervous system, and further discusses the roles of NDRG2 during the occurrence and development of several nervous system diseases.
© The Author 2015. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.
... The expression of Ndrg1 mRNA was by far the most abundant in the kidney ( Figure 1A), and renal expression increased towards the later stage of development ( Figure 1B). Although Wakisaka et al reported that Ndrg1 expression in proximal tubules decreased during maturation in rats [49], immunostaining of Ndrg1 in the mouse kidney demonstrated strong expression in the proximal tubules ( Figures 1C and 1D). Ndrg1 did not co-localize with either calbindin D28K, a marker of the distal convoluted tubule, or USAG-1, a marker of the thick ascending limb and distal convoluted tubule [40] (Figures 1E, 1F, and 1H). ...
Epidemiological findings indicate that acute kidney injury (AKI) increases the risk for chronic kidney disease (CKD), although the molecular mechanism remains unclear. Genetic fate mapping demonstrated that nephrons, functional units in the kidney, are repaired by surviving nephrons after AKI. However, the cell population that repairs damaged nephrons and their repair capacity limitations remains controversial. To answer these questions, we generated a new transgenic mouse strain in which mature proximal tubules, the segment predominantly damaged during AKI, could be genetically labeled at desired time points. Using this strain, massive proliferation of mature proximal tubules is observed during repair, with no dilution of the genetic label after the repair process, demonstrating that proximal tubules are repaired mainly by their own proliferation. Furthermore, acute tubular injury caused significant shortening of proximal tubules associated with interstitial fibrosis, suggesting that proximal tubules have a limited capacity to repair. Understanding the mechanism of this limitation might clarify the mechanism of the AKI-to-CKD continuum.
This article is protected by copyright. All rights reserved.
... NDRG1 is a phosphorylated protein, denoting that the expression and function of NDRG1 may be controlled in part by changes in phosphorylation [2]. NDRG1 was reported to interact with Hsp70 and Hsp90 proteins and play an important biochemical function in cells [3,4]; for example, cell growth and differentiation [5,6] and organ formation [7]. NDRG1 expression was shown to be regulated by several different factors, such as hypoxia [8], differentiationinducing agents [9], oncogenes (N-myc and c-myc) [10,11] and tumor-suppressor genes (p53 and PTEN) [12,13]. ...
N-myc downstream-regulated gene 1 (NDRG1) has been proposed as a tumor suppressor gene in many different types of tumors, but its potential function and corresponding mechanism are not yet fully elucidated. This study aims to detect the possible function of NDRG1 in gastric cancer progression. In this study, 112 paired gastric cancer tissues and corresponding nonmalignant gastric tissues were utilized to identify the differential protein expression of NDRG1 by immunohistochemistry and its clinical significance was analyzed. Furthermore, 49 of 112 paired gastric specimens were used to detect the differential mRNA expression by real-time PCR. The over expression of NDRG1 in human gastric cancer cell line AGS by PcDNA3.1-NDRG1 transfection was utilized to detect the role of NDRG1 in regulating the biological behavior of gastric cancer. NDRG1 expression was significantly decreased in primary gastric cancer tissues, compared with its corresponding nonmalignant gastric tissues (p < 0.05), and its decreased expression was significantly associated with lymph node metastasis (p < 0.01), invasion depth (p < 0.01) and differentiation (p < 0.05). Additionally, the overall survival rate of gastric cancer patients with high expression of NDRG1 was higher than those with low expression during the follow-up period. NDRG1 overexpression suppressed cells proliferation, invasion and induced a G1 cell cycle arrest in gastric cancer. Furthermore, the down-regulation of NDRG1 in gastric cancer metastatic progression was correlated to E-cadherin and MMP-9. Our results verify that NDRG1 acts as a tumor suppressor gene and may play an important role in the metastasis progression and prognosis of gastric cancer.
... g/mL streptomycin, and 100 units/mL penicillin). The pSUPER-NDRG1 vectors were designed as mentioned before1011121314151617 . To establish pSUPER-NDRG1, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCAT- GGGAAC-3' (positions 398-416) and 5'-ATGCAGAG- TAACGTGGAAG-3' (positions 601 to 619), relative to the start codon). ...
... NDRG1 protein expression has been described to be present in normal brain or brain tumor tissue [11] as well as being an important gene that is playing an active role in the regulation of a broad spectrum of human cancer diseases like human gastric cancer, squamous cell carcinomas , breast cancer, human hepatocellular carcinoma, brain tumors and leukemia1213141516171819202122 . NDRG1 was suggested to be a prognostic marker for hypoxic regions within a tumor mass because of its stability as a protein232425 and because it is highly expressed in malignant tumor tissues compared to normal tissue of the same origin [26] . ...
To study short dsRNA oligonucleotides (siRNA) as a potent tool for artificially modulating gene expression of N-Myc down regulated gene 1 (NDRG1) gene induced under different physiological conditions (Normoxia and hypoxia) modulating NDRG1 transcription, mRNA stability and translation.
A cell line established from a patient with glioblastoma multiforme. Plasmid DNA for transfections was prepared with the Endofree Plasmid Maxi kit. From plates containing 5 × 10(7) cells, nuclear extracts were prepared according to previous protocols. The pSUPER-NDRG1 vectors were designed, two sequences were selected from the human NDRG1 cDNA (5'-GCATTATTGGCATGGGAAC-3' and 5'-ATGCAGAGTAACGTGGAAG-3'. reverse transcription polymerase chain reaction was performed using primers designed using published information on β-actin and hypoxia-inducible factor (HIF)-1α mRNA sequences in GenBank. NDRG1 mRNA and protein level expression results under different conditions of hypoxia or reoxygenation were compared to aerobic control conditions using the Mann-Whitney U test. Reoxygenation values were also compared to the NDRG1 levels after 24 h of hypoxia (P < 0.05 was considered significant).
siRNA- and iodoacetate (IAA)-mediated downregulation of NDRG1 mRNA and protein expression in vitro in human glioblastoma cell lines showed a nearly complete inhibition of NDRG1 expression when compared to the results obtained due to the inhibitory role of glycolysis inhibitor IAA. Hypoxia responsive elements bound by nuclear HIF-1 in human glioblastoma cells in vitro under different oxygenation conditions and the clearly enhanced binding of nuclear extracts from glioblastoma cell samples exposed to extreme hypoxic conditions confirmed the HIF-1 Western blotting results.
NDRG1 represents an additional diagnostic marker for brain tumor detection, due to the role of hypoxia in regulating this gene, and it can represent a potential target for tumor treatment in human glioblastoma. The siRNA method can represent an elegant alternative to modulate the expression of the hypoxia induced NDRG1 gene and can help to monitor the development of the cancer disease treatment outcome through monitoring the expression of this gene in the patients undergoing the different therapeutic treatment alternatives available nowadays.
... Although many studies have elucidated the characteristics of Cap43, its exact function remains unclear. Cap43 is expressed in various organs, including the prostate, ovary, colon, and kidney, and its expression changes dynamically during postnatal development in the kidney, brain, liver, and nerves (Lachat et al., 2002;Shimono et al., 1999;Wakisaka et al., 2003). These observations suggested that Cap43 may be involved in normal organ maturation and differentiation. ...
... during normal postnatal development, ndrG1/cap43 is expressed in the membrane and/or cytoplasm of cells in the rat kidney and brain (35). ndrG1/cap43 is also a membrane and/ or cytoplasm protein in human tissues, but its cellular localization is dependent on cell type (35). ...
... during normal postnatal development, ndrG1/cap43 is expressed in the membrane and/or cytoplasm of cells in the rat kidney and brain (35). ndrG1/cap43 is also a membrane and/ or cytoplasm protein in human tissues, but its cellular localization is dependent on cell type (35). For instance, epithelial cells of the prostate predominantly show membranous expression of ndrG1/cap43. ...
Expression of N-myc downstream regulated gene 1 (NDRG1)/Ca(2+)-associated protein 43 (Cap43) in cancer cells is a predictive marker of good or poor prognosis depending on tumor type. In this study, we examined whether NDRG1/Cap43 is a marker of good or poor prognosis in gastric cancer patients, and whether it is associated with tumor stromal responses, including angiogenesis and macrophage infiltration. The expression levels of NDRG1/Cap43, the number of CD68-positive macrophages and the CD34-positive microvessel density were analyzed by immunohistochemistry in 129 gastric cancer patients, including 65 with the intestinal type and 64 with the diffuse type. The expression of NDRG1/Cap43 in the nucleus and the membrane was evaluated. Nuclear NDRG1/Cap43 expression was found in 20/65 (30.8%) patients with the intestinal type and in 9/64 (14.1%) patients with the diffuse type of gastric cancer. Nuclear NDRG1/Cap43 expression was significantly associated with pathological stage in the intestinal type (P=0.002), but not in the diffuse type (P=0.039). Nuclear NDRG1/Cap43 expression was also closely associated with infiltrating macrophages (P=0.001) and tumor angiogenesis (P=0.001) in the intestinal type. Furthermore, nuclear NDRG1/Cap43 expression was associated with poor prognosis in both the intestinal (P=0.001) and the diffuse types of gastric cancer (P=0.047). By contrast, membranous NDRG1/Cap43 expression was not associated with the overall survival of gastric cancer patients with either the intestinal or diffuse type of gastric cancer. The expression of NDRG1/Cap43 in the nucleus may be a predictive biomarker for malignant progression in the intestinal type of gastric cancer, preferable to the expression of NDRG1/Cap43 in the membrane.
